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1.
J Clin Epidemiol ; : 111363, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615828
2.
Stat Methods Med Res ; : 9622802241231496, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502022

RESUMO

Assessing heterogeneity between studies is a critical step in determining whether studies can be combined and whether the synthesized results are reliable. The I2 statistic has been a popular measure for quantifying heterogeneity, but its usage has been challenged from various perspectives in recent years. In particular, it should not be considered an absolute measure of heterogeneity, and it could be subject to large uncertainties. As such, when using I2 to interpret the extent of heterogeneity, it is essential to account for its interval estimate. Various point and interval estimators exist for I2. This article summarizes these estimators. In addition, we performed a simulation study under different scenarios to investigate preferable point and interval estimates of I2. We found that the Sidik-Jonkman method gave precise point estimates for I2 when the between-study variance was large, while in other cases, the DerSimonian-Laird method was suggested to estimate I2. When the effect measure was the mean difference or the standardized mean difference, the Q-profile method, the Biggerstaff-Jackson method, or the Jackson method was suggested to calculate the interval estimate for I2 due to reasonable interval length and more reliable coverage probabilities than various alternatives. For the same reason, the Kulinskaya-Dollinger method was recommended to calculate the interval estimate for I2 when the effect measure was the log odds ratio.

3.
Sci Total Environ ; 926: 171844, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38513844

RESUMO

The composite agent of ferrous sulfate, fly ash, and calcium lignosulfonate (FFC) can remediate the soil contaminated by As and Sb under cyclic freeze-thaw (F-T) via stabilization/solidification (S/S). However, the impact of high-frequency F-T cycles on the leaching behavior and migration of As and Sb in FFC-treated soils remains unclear. Here the leaching concentrations, heavy metal speciation (Wenzel's method), and Hydrus-1d simulations were investigated. The results showed that FFC effectively maintained the long-term S/S efficiency of arsenic remediation subject to an extended rainfall and freeze-thaw cycles, and stabilized the easily mobile form of As. The short-term S/S effect on Sb in the remediated soils suffering from F-T cycles was demonstrated in the presence of FFC. In a 20-year span, the mobility of Sb was affected by the number of F-T cycles (FT60 > FT20 > FT40 > FT0) in soil with a depth of 100 cm. As leaching progressed, FFC slowed the upward proportion of adsorbed As fractions but converted parts of the residual Sb to the form of crystalline Fe/Al (hydro) oxide. Moreover, the adsorption rate and capacity of As also preceded that of Sb. Long-term curative effects of FFC could be observed for As, but further development of agents capable of remedying Sb under cyclic F-T and long-term rainfall was needed. The predictive results on the migration and leaching behavior of heavy metals in S/S remediated soils may provide new insight into the long-term assessment of S/S under natural conditions.

4.
Sci Rep ; 14(1): 5791, 2024 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461342

RESUMO

Diabetic retinopathy (DR) is a serious ocular complication that can pose a serious risk to a patient's vision and overall health. Currently, the automatic grading of DR is mainly using deep learning techniques. However, the lesion information in DR images is complex, variable in shape and size, and randomly distributed in the images, which leads to some shortcomings of the current research methods, i.e., it is difficult to effectively extract the information of these various features, and it is difficult to establish the connection between the lesion information in different regions. To address these shortcomings, we design a multi-scale dynamic fusion (MSDF) module and combine it with graph convolution operations to propose a multi-scale dynamic graph convolutional network (MDGNet) in this paper. MDGNet firstly uses convolution kernels with different sizes to extract features with different shapes and sizes in the lesion regions, and then automatically learns the corresponding weights for feature fusion according to the contribution of different features to model grading. Finally, the graph convolution operation is used to link the lesion features in different regions. As a result, our proposed method can effectively combine local and global features, which is beneficial for the correct DR grading. We evaluate the effectiveness of method on two publicly available datasets, namely APTOS and DDR. Extensive experiments demonstrate that our proposed MDGNet achieves the best grading results on APTOS and DDR, and is more accurate and diverse for the extraction of lesion information.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico por imagem , Olho , Algoritmos , Face , Projetos de Pesquisa
5.
J Am Med Inform Assoc ; 31(5): 1084-1092, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38427850

RESUMO

OBJECTIVE: The aim of this study was to disseminate insights from a nationwide pilot of the International Classification of Diseases-11th revision (ICD-11). MATERIALS AND METHODS: The strategies and methodologies employed to implement the ICD-11 morbidity coding in 59 hospitals in China are described. The key considerations for the ICD-11 implementation were summarized based on feedback obtained from the pilot hospitals. Coding accuracy and Krippendorff's alpha reliability were computed based on the coding results in the ICD-11 exam. RESULTS: Among the 59 pilot hospitals, 58 integrated ICD-11 Coding Software into their health information management systems and 56 implemented the ICD-11 in morbidity coding, resulting in 3 723 959 diagnoses for 873 425 patients being coded over a 2-month pilot coding phase. The key considerations in the transition to the ICD-11 in morbidity coding encompassed the enrichment of ICD-11 content, refinement of tools, provision of systematic and tailored training, improvement of clinical documentation, promotion of downstream data utilization, and the establishment of a national process and mechanism for implementation. The overall coding accuracy was 82.9% when considering the entire coding field (including postcoordination) and 92.2% when only one stem code was considered. Krippendorff's alpha was 0.792 (95% CI, 0.788-0.796) and 0.799 (95% CI, 0.795-0.803) with and without consideration of the code sequence, respectively. CONCLUSION: This nationwide pilot study has enhanced national technical readiness for the ICD-11 implementation in morbidity, elucidating key factors warranting careful consideration in future endeavors. The good accuracy and intercoder reliability of the ICD-11 coding achieved following a brief training program underscore the potential for the ICD-11 to reduce training costs and provide high-quality health data. Experiences and lessons learned from this study have contributed to WHO's work on the ICD-11 and can inform other countries when formulating their transition plan.


Assuntos
Hospitais , Classificação Internacional de Doenças , Humanos , Projetos Piloto , Reprodutibilidade dos Testes , China , Codificação Clínica
6.
iScience ; 27(4): 109358, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38544565

RESUMO

Mesenchymal stem cell (MSC)-mediated coupling of osteogenesis and angiogenesis is a critical phenomenon in bone formation. Herein, we investigated the role and mechanism of SGMS1 in the osteogenic differentiation of MSCs and, in combination with osteogenesis and angiogenesis, to discover new therapeutic targets for skeletal dysplasia and bone defects. SGMS1 addition accelerated MSC osteogenic differentiation, whereas SGMS1 silencing suppressed this process. Moreover, SGMS1 overexpression inhibited ceramide (Cer) and promoted sphingomyelin (SM) levels. SM treatment neutralized the suppressive effect of shSGMS1 on osteogenesis. SGMS1 restrained PP2A activity by regulating Cer/SM metabolism and thus enhanced the levels of phosphorylated Akt, Runx2, and vascular endothelial growth factor (VEGF). Furthermore, SGMS1 transcription was regulated by Runx2. SGMS1 increased MSC-mediated angiogenesis by promoting VEGF expression. SGMS1 addition promoted rat bone regeneration in vivo. In conclusion, SGMS1 induces osteogenic differentiation of MSCs and osteogenic-angiogenic coupling through the regulation of the Cer/PP2A/Akt signaling pathway.

7.
Int Wound J ; 21(2): e14778, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38356179

RESUMO

A meta-analysis was conducted to comprehensively evaluate the impact of wound drainage on postoperative wound infection and healing in patients undergoing spinal surgery. Computer searches were performed, from database inception to October 2023, in EMBASE, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure databases for studies related to the application of wound drainage in spinal surgery. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Overall, 11 articles involving 2102 spinal surgery patients were included. The analysis showed that, compared to other treatment methods, the use of wound drainage in spinal surgery patients significantly shortened the wound healing time (standardized mean difference [SMD]: -1.35, 95% confidence intervals [CI]: -1.91 to -0.79, p < 0.001). However, there was no statistical difference in the incidence of wound infection (odds ratio: 1.35, 95% CI: 0.83-2.19, p = 0.226). This study indicates that wound drainage in patients undergoing spinal surgery is effective, can accelerate wound healing and is worth promoting in clinical practice.


Assuntos
Procedimentos Neurocirúrgicos , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Cicatrização , Fatores de Tempo , Drenagem/métodos
8.
Carbohydr Polym ; 330: 121829, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38368108

RESUMO

The herbal medicine Polygonatum cyrtonema is highly regarded in China for its medicinal and dietary properties. However, further research is needed to elucidate the structure of its polysaccharide and understand how it promotes human health by modulating the gut microbiota. This study aims to investigate a homogeneous polysaccharide (PCP95-1-1) from Polygonatum cyrtonema and assess its susceptibility to digestion as well as its utilization by intestinal microbiota. The results confirmed that PCP95-1-1 is an agavin-type fructan, which possesses two fructose chains, namely ß-(2 â†’ 6) and ß-(2 â†’ 1) fructosyl-fructose, attached to the sucrose core, and has branches of ß-D-Fruf residues. Moreover, PCP95-1-1 demonstrated resistance to digestion and maintained its reducing sugar content throughout the digestive system, indicating it could reach the gut without being digested. In vitro fermentation of PCP95-1-1 significantly decreased the pH value (p < 0.05) while notably increasing the production of short-chain fatty acids (SCFAs), confirming its utilization by human gut microbiota. Additionally, PCP95-1-1 exhibited a significant ability (p < 0.05) to beneficial bacteria such as Megamonas and Bifidobacterium, while reducing the presence of facultative or conditional pathogens such as Escherichia-Shigella and Klebsiella at the genus level. Consequently, PCP95-1-1 has the potential to positively influence physical well-being by modulating the gut microbiota environment and can be developed as a functional food.


Assuntos
Microbioma Gastrointestinal , Polygonatum , Humanos , Frutanos/farmacologia , Polygonatum/química , Polissacarídeos , Frutose
9.
Target Oncol ; 19(1): 81-93, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38265547

RESUMO

BACKGROUND: The prognostic impact of HER2-low on overall survival (OS) and disease-free survival (DFS) in patients with resectable breast cancer (BC) remains controversial, partly resulting from the hormone receptor (HR) status. OBJECTIVE: To investigate the prognostic impact of HER2-low in different HR subgroups. PATIENTS AND METHODS: We retrospectively retrieved medical records of treatment-naive primary HER2-low and HER2-zero BC patients who were diagnosed with invasive ductal carcinoma and underwent surgery in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2009 to September 2017 (n = 7371). We compared the clinicopathologic features and performed Cox regression and landmark survival analyses to explore the prognostic impact of HER2-low on survival outcomes during distinct post-surgery intervals-36 months, 60 months, and 120 months. RESULTS: HER2-low BC, compared to HER2-zero BC, exhibited less aggressive clinicopathologic features, such as smaller invasion size, lower grade, increased nerve invasion, higher HR positivity, and a higher proportion of low-Ki67 cases. In the HR-positive subgroup, HER2-low demonstrated improved OS (p = 0.046) and DFS (p = 0.026) within 60 months. Conversely, HER2-low displayed worse DFS (p = 0.046) in the HR-negative subgroup after 36 months from surgery. The findings remained robust in uni- and multi-variable Cox models. CONCLUSIONS: HER2-low BCs manifested less aggressive clinicopathologic features than the HER2-zero cases. The prognostic impact of HER2-low in resectable BCs exhibits variability contingent upon the patients' HR status.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Prognóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptor ErbB-2 , Estudos Retrospectivos , Hormônios
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(1): 20-24, 2024 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-38171554

RESUMO

OBJECTIVE: To assess the effectiveness and feasibility of carrier detection for Spinal muscular atrophy (SMA) by using digital PCR assay. METHODS: Peripheral blood samples were collected from 214 pregnant women who were routinely screened for SMA carriers, of which 204 were randomly selected samples and 10 were samples with known copy numbers of SMN1 exons 7 and 8. Samples with known copy numbers of SMN1 exons 7 and 8 were randomly mixed into the experiment to validate the performance of the digital PCR assay. RESULTS: The copy numbers of SMN1 exons 7 and 8 and SMN2 exons 7 and 8 in peripheral blood samples were detected by digital PCR assay. The results of SMN1 exons 7 and 8 were compared with those of the quantitative PCR method to assess the reliability and clinical performance of the digital PCR assay. Among the 204 random samples, digital PCR has detected five samples with simultaneous heterozygous deletion of SMN1 exons 7 and 8, three samples with heterozygous deletion of SMN1 exon 8 only, and 196 samples with no deletion of SMN1 exons 7 and 8. Ten samples with known SMN1 exons 7 and 8 copy numbers were detected with the expected values. The digital PCR test results were fully consistent with that of the quantitative PCR. CONCLUSION: The results of digital PCR for the detection of copy number variation of SMN1 exons 7 and 8 were consistent with qPCR. Digital PCR assay was able to clearly distinguish the copy number of the target genes, therefore can be used for SMA carrier screening. Moreover, it can also detect copy number of SMN2 exons 7 and 8, which can provide more information for genetic counseling.


Assuntos
Variações do Número de Cópias de DNA , Atrofia Muscular Espinal , Humanos , Feminino , Gravidez , Reprodutibilidade dos Testes , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Reação em Cadeia da Polimerase/métodos , Técnicas de Amplificação de Ácido Nucleico , Proteína 1 de Sobrevivência do Neurônio Motor/genética
11.
Sci Total Environ ; 914: 169803, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38181949

RESUMO

The wild yak (Bos mutus) is a cold-tolerant herbivore native to the Tibetan Plateau and has been categorized as vulnerable by the International Union for Conservation of Nature and Natural Resources. Low population densities within currently fragmented habitats and unclear landscape conservation priorities warrant attention. Herein, we employed the maximum entropy (MaxEnt) model using over 900 wild yak occurrence records to model wild yak habitat suitability. Our analysis revealed unprotected wild yak landscapes covering 30.79 % of the habitat area, indicating a conservation gap between protected areas (PAs) and wild yak habitats. To protect metapopulation dynamics and mitigate high risks of poaching, habitat degradation and fragmentation, resource competition, and degenerated genetic characterization of wild yaks in fragmented and degraded habitat, we identified eight habitat patches as landscape conservation units (LCUs) and 14 linkages among the LCUs, enhancing the connectivity between LCUs to decrease negative effects of genetic threats. A centrality analysis demonstrated that Changtang, Arjinshan, and Hoh Xil national nature reserves and their linkages are all critical for the maintenance of habitat connectivity. Here, we suggest that habitat- and LCU-specific conservation strategies should be highlighted during the establishment of PAs and transboundary cooperation. Ultimately, our results can assist conservationists and land managers in comprehending wild yak distribution, movement, and habitat requirements, as well as for the development of effective protection strategies. Furthermore, the combined modeling method (MaxEnt-Zonation-InVEST) could be utilized as a component for identifying conservation priorities and linkages between core patches for species and assessing the efficiency of PAs, core habitats, and corridors in achieving conservation goals. Our study can provide a framework in identifying priority conservation and connectivity between habitat patches to facilitate effectively conservation and genetic resilience for endangered species in fragmented habitats.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Animais , Bovinos , Tibet , China , Espécies em Perigo de Extinção
12.
Med Res Rev ; 44(2): 606-631, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37947371

RESUMO

Breast cancer (BC) constitutes one of the most pervasive malignancies affecting the female population. Despite progressive improvements in diagnostic and therapeutic technologies, leading to an increased detection of early stage BCs, locally advanced breast cancer (LABC) persists as a significant clinical challenge. Owing to its poor overall survival (OS) rate, elevated recurrence rate, and high potential for distant metastasis, LABC prominently impacts the comprehensive efficacy of BC treatments. Radiotherapy, encompassing preoperative, intraoperative, and postoperative modalities, is acknowledged as an effective strategy for mitigating BC metastasis and enhancing survival rates among patients. Nevertheless, the domain of preoperative neoadjuvant radiotherapy (NART) remains conspicuously underexplored in clinical studies. Available research suggests that NART can induce tumor volume reduction, provoke fibrotic changes in tumor and adjacent normal tissues, thereby mitigating intraoperative cancer propagation and enhancing the quality of life for LABC patients. This manuscript seeks to provide a review of contemporary research pertaining to LABC and its preoperative radiotherapy.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Qualidade de Vida
13.
Angle Orthod ; 94(1): 68-74, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37839805

RESUMO

OBJECTIVES: To determine the optimal settings for reconstructing the buccal surfaces of different tooth types using the virtual bracket removal (VBR) technique. MATERIALS AND METHODS: Ten postbonded digital dentitions (with their original prebonded dentitions) were enrolled. The VBR protocol was carried out under five settings from three commonly used computer-aided design (CAD) systems: OrthoAnalyzer (O); Meshmixer (M); and curvature (G2), tangent (G1), and flat (G0) from Geomagic Studio. The root mean squares (RMSs) between the reconstructed and prebonded dentitions were calculated for each tooth and compared with the clinically acceptable limit (CAL) of 0.10 mm. RESULTS: The overall prevalences of RMSs below the CAL were 66.80%, 70.08%, 62.30%, 94.83%, and 56.15% under O, M, G2, G1, and G0, respectively. For the upper dentition, the mean RMSs were significantly lower than the CAL for all tooth types under G1 and upper incisors and canines under M and G2. For the lower dentition, the mean RMSs were significantly lower than the CAL for all tooth types under G1 and lower incisors and canines under M, G2, and G0 (all P < .05). Additionally, the mean RMSs of all teeth under G1 were significantly lower than those under the other settings (all P < .001). CONCLUSIONS: The optimal settings varied among different tooth types. G1 performed best for most tooth types compared to the other four settings.


Assuntos
Incisivo , Raiz Dentária , Desenho Assistido por Computador
14.
Med Res Rev ; 44(1): 275-364, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37621230

RESUMO

Reactive oxygen species (ROS) are produced during oxidative metabolism in aerobic organisms. Under normal conditions, ROS production and elimination are in a relatively balanced state. However, under internal or external environmental stress, such as high glucose levels or UV radiation, ROS production can increase significantly, leading to oxidative stress. Excess ROS production not only damages biomolecules but is also closely associated with the pathogenesis of many diseases, such as skin photoaging, diabetes, and cancer. Antioxidant peptides (AOPs) are naturally occurring or artificially designed peptides that can reduce the levels of ROS and other pro-oxidants, thus showing great potential in the treatment of oxidative stress-related diseases. In this review, we discussed ROS production and its role in inducing oxidative stress-related diseases in humans. Additionally, we discussed the sources, mechanism of action, and evaluation methods of AOPs and provided directions for future studies on AOPs.


Assuntos
Antioxidantes , Estresse Oxidativo , Humanos , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico , Oxirredução
15.
Int J Antimicrob Agents ; 63(2): 107065, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38122947

RESUMO

The emergence of Acinetobacter baumannii infections as a significant healthcare concern in hospital settings, coupled with their association with poorer clinical outcomes, has prompted extensive investigation into novel therapeutic agents and innovative treatment strategies. Proguanil and chlorhexidine, both categorized as biguanide compounds, have displayed clinical efficacy as antimalarial and topical antibacterial agents, respectively. In this study, we conducted an investigation to assess the effectiveness of combining proguanil and chlorhexidine with clarithromycin or rifampicin against both laboratory strains and clinical isolates of A. baumannii. The combination therapy demonstrated rapid bactericidal activity against planktonic multidrug-resistant A. baumannii, exhibiting efficacy in eradicating mature biofilms and impeding the development of antibiotic resistance in vitro. Additionally, when administered in conjunction with clarithromycin or rifampicin, proguanil enhanced the survival rate of mice afflicted with intraperitoneal A. baumannii infections, and chlorhexidine expedited wound healing in mice with skin infections. These findings are likely attributable to the disruption of A. baumannii cell membrane integrity by proguanil and chlorhexidine, resulting in heightened membrane permeability and enhanced intracellular accumulation of clarithromycin and rifampicin. Overall, this study underscores the potential of employing proguanil and chlorhexidine in combination with specific antibiotics to effectively combat A. baumannii infections and improve treatment outcomes in clinically challenging scenarios.


Assuntos
Acinetobacter baumannii , Rifampina , Animais , Camundongos , Rifampina/farmacologia , Rifampina/uso terapêutico , Clorexidina/farmacologia , Clorexidina/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Proguanil/farmacologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla
16.
Front Microbiol ; 14: 1304874, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38116529

RESUMO

Myxococcus xanthus and Escherichia coli represent a well-studied microbial predator-prey pair frequently examined in laboratory settings. While significant progress has been made in comprehending the mechanisms governing M. xanthus predation, various aspects of the response and defensive mechanisms of E. coli as prey remain elusive. In this study, the E. coli MG1655 large-scale chromosome deletion library was screened, and a mutant designated as ME5012 was identified to possess significantly reduced susceptibility to predation by M. xanthus. Within the deleted region of ME5012 encompassing seven genes, the significance of dusB and fis genes in driving the observed phenotype became apparent. Specifically, the deletion of fis resulted in a notable reduction in flagellum production in E. coli, contributing to a certain level of resistance against predation by M. xanthus. Meanwhile, the removal of dusB in E. coli led to diminished inducibility of myxovirescin A production by M. xanthus, accompanied by a slight decrease in susceptibility to myxovirescin A. These findings shed light on the molecular mechanisms underlying the complex interaction between M. xanthus and E. coli in a predatory context.

17.
Cell Death Discov ; 9(1): 404, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907480

RESUMO

Hippocampal neuronal damage may induce cognitive impairment. Neurotrophic tyrosine kinase receptor 1 (NTRK1) reportedly regulates neuronal damage, although the underlying mechanism remains unclear. The present study aimed to investigate the role of NTRK1 in mouse hippocampal neuronal damage and the specific mechanism. A mouse NTRK1-knockdown model was established and subjected to pre-treatment with BAY-3827, followed by a behavioral test, Nissl staining, and NeuN immunofluorescence (IF) staining to evaluate the cognitive impairment and hippocampal neuronal damage. Next, an in vitro analysis was conducted using the CCK-8 assay, TUNEL assay, NeuN IF staining, DCFH-DA staining, JC-1 staining, ATP content test, mRFP-eGFP-LC3 assay, and LC3-II IF staining to elucidate the effect of NTRK1 on mouse hippocampal neuronal activity, apoptosis, damage, mitochondrial function, and autophagy. Subsequently, rescue experiments were performed by subjecting the NTRK1-knockdown neurons to pre-treatment with O304 and Rapamycin. The AMPK/ULK1/FUNDC1 pathway activity and mitophagy were detected using western blotting (WB) analysis. Resultantly, in vivo analysis revealed that NTRK1 knockdown induced mouse cognitive impairment and hippocampal tissue damage, in addition to inactivating the AMPK/ULK1/FUNDC1 pathway activity and mitophagy in the hippocampal tissues of mice. The treatment with BAY-3827 exacerbated the mouse depressive-like behavior induced by NTRK1 knockdown. The results of in vitro analysis indicated that NTRK1 knockdown attenuated viability, NeuN expression, ATP production, mitochondrial membrane potential, and mitophagy, while enhancing apoptosis and ROS production in mouse hippocampal neurons. Conversely, pre-treatment with O304 and rapamycin abrogated the suppression of mitophagy and the promotion of neuronal damage induced upon NTRK1 silencing. Conclusively, NTRK1 knockdown induces mouse hippocampal neuronal damage through the suppression of mitophagy via inactivating the AMPK/ULK1/FUNDC1 pathway. This finding would provide insight leading to the development of novel strategies for the treatment of cognitive impairment induced due to hippocampal neuronal damage.

18.
Biomed Pharmacother ; 169: 115920, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37995565

RESUMO

Neurological disorders affect a large population, often leading to different levels of disability and resulting in decreased quality of life. Due to the limited recovery obtained from surgical procedures and other medical approaches, a large number of patients with prolonged dysfunction receive neurorehabilitation protocols to improve their neural plasticity and regeneration. However, the poor neural regeneration ability cannot effectively rebuild the tissue integrity and neural functional networks; consequently, the prognoses of neurorehabilitation remain undetermined. To increase the chances of neural regeneration and functional recovery for patients with neurological disorders, regenerative rehabilitation was introduced with combined regenerative medicine and neurorehabilitation protocols to repair neural tissue damage and create an optimized biophysical microenvironment for neural regeneration potential. With the deepening of exosome research, an increasing number of studies have found that the systemic therapeutic effects of neurorehabilitation approaches are mediated by exosomes released by physically stimulated cells, which provides new insight into rehabilitative mechanisms. Meanwhile, exosome therapy also serves as an alternative cell-free therapy of regenerative medicine that is applied in partnership with neurorehabilitation approaches and formulates exosome-based neurological regenerative rehabilitation. In this study, we review the current state of exosome-associated neurorehabilitation. On the one hand, we focus on presenting the varied mediating effects of exosomes in neurorehabilitation protocols of specific neurological pathologies; on the other hand, we discuss the diverse combinations of exosome therapies and neurorehabilitation approaches in the field of neurological regenerative rehabilitation, aiming to increase the awareness of exosome research and applications in the rehabilitation of neurological disorders.


Assuntos
Exossomos , Doenças do Sistema Nervoso , Humanos , Gelo , Qualidade de Vida , Doenças do Sistema Nervoso/terapia , Medicina Regenerativa/métodos
19.
Future Oncol ; 19(36): 2405-2416, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38018520

RESUMO

Background: This single-center retrospective study compared the efficacy of breast-conserving therapy along with axillary lymph node dissection (ALND) with mastectomy and ALND with regard to survival of Chinese patients with occult breast cancer. Materials & methods: Univariate Kaplan-Meier analysis and multivariate Cox proportional hazards model were used to compare treatments and prognosis. Results: A total of 111 patients with a median follow-up of 72.9 months were included. 39 patients with mastectomy + ALND had better disease-free survival than 72 patients with breast-conserving therapy + ALND (HR = 0.31; p = 0.012). Patients with radiotherapy demonstrated inferior survival for both overall survival (HR = 2.67; p = 0.071) and disease-free survival (HR = 5.35; p = 0.002). Surgical strategies and radiotherapy remained significantly predictive of better disease-free survival in multivariate analyses. Conclusion: Mastectomy and ALND demonstrate superior disease-free prognosis compared with breast-conserving therapy and ALND in occult breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Mastectomia , Estudos Retrospectivos , Prognóstico , Mastectomia Segmentar , Excisão de Linfonodo/efeitos adversos , Biópsia de Linfonodo Sentinela
20.
PLoS One ; 18(9): e0291363, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37682981

RESUMO

Cordyceps militaris is a medicinal mushroom and has been extensively used as a traditional medicine in East Asia. After the chrysalis seeds are matured and harvested, the spent substrate of C. militaris still contains active ingredients but is usually discarded as waste. This study aimed to determine the antioxidant and anti-inflammatory activities of C. militaris spent substrate extract and its inhibitory activity on the Malassezia commensal yeasts that can cause dandruff and seborrheic dermatitis. Active substances in the spent substrate of C. militaris were extracted using a hot water extraction method and were used for the determination of antioxidant activity by measuring their ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radicals, hydrogen peroxide, and superoxide anions. The ability to inhibit Malassezia was analyzed using the broth microdilution method, and the reparative effect on oxidative damage in HaCaT cells was measured using in vitro cell analysis. Respiratory burst evaluation was used to determine the anti-inflammatory capacity of extracts. Analysis of the Malassezia-inhibiting activity of the extracts showed that the minimum inhibitory concentration was 6.25 mg/mL. The half maximal inhibitory concentration (IC50) values of DPPH, O2-, H2O2 and OH- were 3.845 mg/mL, 2.673 mg/mL, 0.037 mg/mL and 0.046 mg/mL, respectively. In the concentration range of 2 to 50%, the extract was non-toxic to cells and was able to protect HaCaT cells from H2O2 damage. When the volume fraction of the extract was 20.96%, its anti-inflammatory ability reached 50%. These results demonstrated that the extract may be a safe and efficacious source for pharmaceutical or cosmetic applications, with Malassezia-inhibiting, antioxidant and anti-inflammatory activities.


Assuntos
Anti-Infecciosos , Antineoplásicos , Cordyceps , Malassezia , Antioxidantes/farmacologia , Peróxido de Hidrogênio , Anti-Inflamatórios/farmacologia
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